Study in South African township shows HIV-negative individuals often source of new TB cases in patients with HIV

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HIV-negative individuals are an important source of new tuberculosis (TB) cases in people living with HIV, according to a study conducted in a South African township published in the online edition of the Journal of Infectious Diseases.

The authors examined TB isolates obtained from sputum samples to see if cases were reactivation of latent disease, unique cases, index cases within clusters, or secondary transmissions within clusters. Cluster index cases were significantly more likely to be HIV-negative and secondary cases within clusters were significantly more likely to involve people living with HIV, including people on antiretroviral therapy (ART).

“Cluster analysis showed that HIV-positive and HIV-negative TB disease are not independent of one another,” write the authors. “Cluster index patients had nearly twice the odds of being HIV-negative suggesting that HIV-negative patients may be disproportionally responsible for transmission in the community.”


transmission cluster

By comparing the genetic sequence of the virus in different individuals, scientists can identify viruses that are closely related. A transmission cluster is a group of people who have similar strains of the virus, which suggests (but does not prove) HIV transmission between those individuals.


A variant characterised by a specific genotype.



The study of the causes of a disease, its distribution within a population, and measures for control and prevention. Epidemiology focuses on groups rather than individuals.

molecular surveillance

The use of data collected during routine drug resistance testing to compare the genetic sequence of the virus in a population and identify transmission clusters. This may allow public health officials to identify populations where transmission is occurring rapidly, indicating gaps in health services that need be addressed.

drug interaction

A risky combination of drugs, when drug A interferes with the functioning of drug B. Blood levels of the drug may be lowered or raised, potentially interfering with effectiveness or making side-effects worse. Also known as a drug-drug interaction.

TB remains an important cause of serious illness and death in resource-limited settings. The burden of TB disease is especially high in countries with serious HIV epidemics.

A better understanding of the dynamics of TB transmission is required so that more effective infection control strategies can be developed. A technique called molecular epidemiology can be used to trace the dynamics of TB transmissions. It involves the genetic analysis of isolates obtained from patients to see if their infection can be linked to other cases.

An international team of investigators used molecular epidemiology to explore the interaction between TB disease in HIV-positive and HIV-negative patients, and also to examine the impact of antiretroviral therapy programmes on the dynamics of TB transmission.

TB isolates were collected from people living in a South African township. Approximately a quarter of adults resident in the township are living with HIV. TB notification rates are extraordinarily high at over 2000 cases per 100,000 and the annual risk of TB infection is 4%.

Analysis of TB genotypes from isolates enabled the investigators to determine if cases were reactivation of latent disease, unique cases, index cases in clusters, or secondary transmissions within clusters.

The study population comprised 710 people who received care between 2001 and 2010. The median age was 32 years. Most (91%) patients were tested for HIV and 64% were HIV-positive, with 23% taking ART at the time of TB diagnosis.

The patients provided 718 isolates from which 318 TB genotypes were identified.

The dominant TB strains were W-Beijing (32%), CC-related (30%) and BM (5%). Comparison with other strains showed that W-Beijing strain was associated with HIV infection (p = 0.001).

Of the 718 TB isolates, 31% were unique strains, 67% were clustered and 2% were reactivation disease. There were a total of 87 clusters within the community, their size ranging from 2 to 85 patients.

The majority of cluster index patients (66%) were HIV negative, whereas two-thirds (63%) of secondary cases within clusters were HIV positive. At least 61% of clusters involved both HIV-positive and HIV-negative patients, with a further 9% possibly including patients with and without HIV.

There was substantial evidence that HIV-negative individuals were the source of new TB infections in people living with HIV. Index cases were almost twice as likely to be HIV negative compared with other TB cases (OR = 1.9; 95% CI, 1.2-31.) Reactivation cases were also more likely to occur in HIV-negative patients (OR = 1.7; 95% CI, 1.2-2.4). Secondary cluster cases were more likely to involve HIV-positive patients (p = 0.001) and patients on ART (p = 0.04).

“Recent transmission was responsible for as much as 54% of the overall TB disease and 60% among HIV-positive patients,” comment the investigators. “HIV-negative patients accounted for a disproportionally high number of cluster index cases.”

The authors suggest their findings have important implications for TB control. “Our attention and interventions need to expand beyond HIV-positive patients, and include reducing transmission from HIV-negative patients,” they conclude. “Such efforts may be guided by the identification of the factors and locations associated with transmission in these settings.”


Middelkoop K et al. Transmission of TB in a high HIV prevalent South African community. J Infect Dis. Online edition, 2014.